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2A week 2 - coagulation and bone marrow disease > haematopoiesis, stem cells and bone marrow > Flashcards

haematopoiesis, stem cells and bone marrow Flashcards

1
Q

what are pluripotent stem cells

A

completelty undifferentiated stem cells - can form any tissue in the body

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2
Q

what kind of stem cells are harmatopoietic stem cells

A

multi potent

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3
Q

where are adult haematopoietic stem cells found

A

bone marrow

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4
Q

haematopoetic stem cell differentiation pathways (3)

A
  1. stem cell -> myeloid stem cell -> myeloblast -> granulocytes (eosinophils, neutrophils, basophils etc.);
  2. stem cell -> myeloid stem cell -> RBC;
  3. stem cell -> lymphoid stem cell -> lymphoblast -> B/T lymphocyte, NK cells
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5
Q

where is blood formed in the foetus

A

yolk sac

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6
Q

what is red marrow

A

the bone marrow that contains blood stem cells

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7
Q

what happens to red marrow as ppl age

A

it is replaced by yellow marrow (fatty tissue) and haematopoiesis is restricted to the axial skeleton

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8
Q

what is extramedullary haematopoeisis and when does to occur

A

when the liver and spleen are recruited to produce blood cells (yellow marrow may also be converted back to red); occurs under stress e.g. myelofibrosis

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9
Q

what is myelofibrosis

A

bone marrow cancer that leads to the occupation of bone marrow space with fibrotic tissue -> no space for blood cell production and so body compensates by producing it else where (liver, spleen) -> enlargement of these organs is seen

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10
Q

what are platelets formed from

A

they are small particles of cytoplasm that have budded off from megakaryocyte cells (they are not themselves cells)

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11
Q

2 common properties of stem cells

A

the ability to self re-new; ability to differentiate into more specialised cells

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12
Q

what determines the function of the stem cell (proliferation vs specialisation)

A

the micro environment - growth factors and interactions with neighboring cells determine the type of cell division the stem cell undergoes (symmetric to form specialised cells or asymmetric for self renerwal)

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13
Q

components of the blood in a centrifuge (bottom to top)

A

erythrocytes (45%) -> buffy coat (platelets +WBCs) ->plasma

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14
Q

volume of blood in an avg man/women

A

man - 5/6L
women - 4/5L depending on body size, during pregnancy this can increase by 50%

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15
Q

features of a neutrophil on a blood film

A

purple granules; lobed nucleus (2-5 lobes)

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16
Q

features of an eosinophil on a blood film

A

large cell, brick-red granules (acidic stain taken up), lobed nucleus (2 lobes)

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17
Q

features of a basophil on a blood film

A

stain blue (basic stain taken up)

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18
Q

features of a lymphocyte on a blood film

A

small; small spherical nucleus which stains darkly

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19
Q

features of a monocyte on a blood film

A

largest WBC, kidney bean shaped nucleus, abundant cytoplasm with pink/purple granules, vacuole often present

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20
Q

what are the important haematopoietic growth factors (4)

A
  1. erythropoetin -rbc production, released from kidney;
  2. thrombopoetin - produced by liver and kidney;
  3. granulocyte colony stimulating factor (GCSF) - produced by endothelium;
  4. interleukins/cytokines - released by immune cells to promote further immune cell differentiation
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21
Q

what causes stimulation of erythropoietin

A

low blood oxygen

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22
Q

what suppresses erythropoietin synthesis

A

increase in oxygen carrying capacity of the blood (incr. O2 levels)

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23
Q

2 causes of high blood counts

A

primary - abnormal bone marrow and the usual mechanisms that control cell production/inhibit proliferation have been overcome i.e. cancer;

secondary - normal bone marrow that is being stimulated by environmental factors to produce more cells

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24
Q

leucocytosis causes (primary, secondary)

A

primary - clonal stem cell disorder, usually in pts w leukaemia, lymphoma and myeloproliferative disorders;

secondary - response to environment e.g. infection, chronic inflammation states, post infarction, other tumours

25
Q

causes of thrombocytosis (primary, secondary)

A

primary - thrombocythemia (clonal cell disorder);
secondary - response to environment e.g. infection, inflammation, infarction, tumour

26
Q

what is primary thrombocytosis treated with

A

a chemotherapy agent - hydroxycarbamide (+ aspirin due to incr risk of thrombosis)

27
Q

what is the haematocrit (+usual value)

A

the ratio of RBCs to total blood volume - usually 40-45%

28
Q

polycythemia vs erythrocytosis

A

polycythemia - any increase in hematocrit and/or hemoglobin;
erythrocytosis - an increase specifically in the number of red blood cells in the blood

29
Q

what is a pt at risk of with polycythemia

A

increase risk of thrombosis - blood is thicker

30
Q

what is apparent polycythemia and what are its causes (4)

A

a raised Hct despite a normal/minimally raised red cell volume due to a reduced plasma volume;
causes - smoking, excess alcohol, drugs (diuretics), being overweight

31
Q

causes of erythrocytosis (primary, secondary)

A

primary - polycythemia vera (mutuaiton in JAK2 gene);
secondary - raised erythropoietin levels due to low O2 (e.g. COPD), tumours (some secrete epo, esp lung and renal), doping, high affinity Hb variant

32
Q

how is polycythemia vera treated

A

hydroxycarbamide + aspirin or venesection + aspirin

33
Q

2 main causes of low blood cell counts

A
  1. underproduction
  2. reduced survival in circulation
34
Q

causes of leukocytopenia

A

underporduction - drugs affecting stem cells, part of pancytopenia due to marrow failure;
reduced survivial - autoimmune, drugs, consumption (while fighting an infection), combination (e.g. viral hepatitis)

35
Q

causes of Thrombocytopenia

A

underproduction - drugs affecting stem cells, liver failure (↓TPO produciton), part of pancytopenia due to marrow failure;
peripheral destruction - autoimmune (e.g. ITP), hypersplenism, drugs (e.g. NSAIDs), infection/inflammation/sepsis

36
Q

6 malignant conditions that cause reduced blood cell production (+2 other non malignant causes)

A
  1. myeloma (plasma cells);
  2. myelodysplasia (myeloid cells);
  3. metastatic malignancy;
  4. myelofibrosis (haemopoetic stem cells);
  5. leukaemia (WBCs, over produciton of one type is a detriment to all others)
  6. lymphoma (lymphocytes + lymphatic system)
  7. aplastic anaemia (empty bone marrow due to stem cell failure)
  8. haematinic deficiency (check for B12/folate levles)
37
Q

what defines acute myeloid leukemia on a blood film

A

the presence of myeloblasts - immature precursors that get stuck in this point of differentiation

38
Q

what are the myeloid cell malignancies (important!)

A

immature cells (blasts) - acute myeloid leukaemia;
mature cells - myeloproliferative disorders (polycythemia vera, chronic myeloid leukemia, essential thrombocythaemia, myelofibrosis), myelodysplasia

39
Q

lymphoid cell malignancies (important!!)

A

immature cells - acute lymphoblastic leukaemia;
mature cells - chronic lymphocytic leukaemia, lymphoma, myeloma

40
Q

what is special about myelodysplasia

A

there is abnormal maturation and proliferation (not just one)

41
Q

what causes aplastic anaemia

A

damage to pluripotent/multipotent stem cell by drugs, viruses, radiation, immune suppression etc.

42
Q

aplastic anaemia blood test findings

A

pancytopenia, reduced reticulocyte count

43
Q

myelofibrosis pathophys

A

malignant proliferation of reticulin fibres in bone marrow resulting in anaemia + splenomegaly

44
Q

what is seen on a myelofibrosis blood film

A

leucoerythroblastic blood film - immature RBCs and WBCs in the peripheral blood

45
Q

what can myelofibrosis develop secondary to

A

myeloproliferative neoplasms -> thye pt may have had polycythemia vera or essential thrombocythemia first

46
Q

what can myelofibrosis transform into

A

myeloid leukaemia

47
Q

4 causes of low blood count with normal bone marrow (i.e. reduced cell survival cause)

A
  1. immune cellular destruciton;
  2. drugs;
  3. haemorrhage;
  4. hypersplenism
48
Q

examples of autoimmune conditions resulting in low blood counts (3)

A

Immune thrombocytopenia (ITP); AIHA; autoimmune neutropenia

49
Q

what is an auer rod

A

pink needle-shaped structures resulting from an abnormal fusion of azurophilic granules - typically found in acute myeloid leukemia

50
Q

4 causes for hyposplenism

A
  1. splenectomy (therapeutic for a blood disorder, trauma);
  2. auto-infarction (sickle cell);
  3. infiltration (metastatic malignancy);
  4. underfunctioning (e.g. coeliac disease)
51
Q

what is the hallmark of hyposplenism on a blood film

A

Howell-Jolly bodies (remnants of RBC nuclei that are normally removed by the spleen)

52
Q

8 causes of neutrophilia

A
  1. bacterial infection;
  2. inflammatory conditions;
  3. burns;
  4. cigarette smoking;
  5. steroids;
  6. granulocyte colony stimulating factor (G-CSF);
  7. solid tumours;
  8. myeloproliferative disorders (CML etc.)
53
Q

how does chronic myeloid leukemia cause neutrophilia

A

expansion of the myeloid lineage which results in neutrophiliaa

54
Q

6 causes of lymphocytosis

A
  1. viral infection (EBV) - most common;
  2. hyposplenism;
  3. TB;
  4. brucellosis;
  5. CLL;
  6. lymphoma with “spillover”
55
Q

5 causes of eosinophilia

A
  1. allergic reactions;
  2. vasculitis;
  3. drugs;
  4. worm infestations;
  5. cancer
56
Q

why should blood test results be compared to past tests

A

to see if the abnormality is new or lifelong

57
Q

what is aquagenic pruritus and what is it associated with

A

a skin disease characterized by the development of severe itching on contact with water without observable skin lesions - assoicated with polycythemia (rubra) vera

58
Q

what can cause failure of blood cell production (4)

A
  1. hornome deficiency;
  2. marrow infiltration;
  3. toxic effects of alcohol/infection/drugs;
  4. marrow aplasia
59
Q

what can cause ineffective blood cell production (4)

A
  1. iron deficiency;
  2. B12/folate deficiency;
  3. myelodysplasia;
  4. thalassaemia major

2A week 2 - coagulation and bone marrow disease (8 decks)

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